tbuckley/cabot-search huggingface dataset:
Network meta-analysis of progression free survival in the treatment of relapsed or refractory chronic lymphocytic leukemia.
Authors: Asher Chanan-Khan, Tom Liu, Keri Yang, Aileen Cohen, Kyle Fahrbach, Joanna Campbell, Boxiong Tang
Journal: Journal of Clinical Oncology (2022)

e19514 Background: Zanubrutinib, a next-generation Bruton’s tyrosine kinase inhibitor (BTKi), demonstrated superior overall response rate and a trend toward improved progression-free survival (PFS) as compared to ibrutinib in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) in the phase 3 ALPINE trial (NCT03734016) based on interim analysis. However, its comparative efficacy with other treatments is not known. The goal of this study was to estimate the relative efficacy of zanubrutinib compared with standard treatments for R/R CLL through a network meta-analysis (NMA). Methods: The efficacy of zanubrutinib from ALPINE (study of zanubrutinib and ibrutinib in patients with R/R CLL was compared to ibrutinib, acalabrutinib, bendamustine and rituximab (BR), and venetoclax + rituximab (V+R) using data from 4 RCTs. Relevant RCTs were identified using a systematic literature review. A network was constructed that composed RCTs (ALPINE, ELEVATE-RR [NCT02477696], ASCEND [NCT02970318], and MURANO [NCT02005471]). Bayesian network meta-analysis (NMA) models were used to simultaneously synthesize hazard ratios (HRs) and 95% credible intervals (CrIs) for investigator-assessed PFS and overall survival (OS) to estimate the relative efficacy of zanubrutinib versus comparators of interest. An assumption of constant hazard ratio was applied in the NMA analysis. Analyses were performed using well-established codes published by the National Institute for Health and Care Excellence (NICE) Decision Support Unit and were implemented with OpenBUGS (version 3.2.3). Results: The NMA suggested a significant improvement in PFS for zanubrutinib over acalabrutinib (HR=0.52, 95% CrI [0.30, 0.90]), ibrutinib (0.47, [0.29, 0.76]), and BR (0.13, [0.06, 0.26]). Zanubrutinib had a numerically better PFS than V+R (0.69, [0.32, 1.46]) while not reaching statistical significance. For OS, NMA results showed a trend favoring zanubrutinib over acalabrutinib (0.75, [0.35, 1.59]), ibrutinib (0.62, [0.31, 1.22]), and BR (0.52, [0.21, 1.24]). The difference was not statistically significant with wide CrIs, suggesting a high uncertainty as inherent limitation of the analysis. Conclusions: This NMA reports the first summary of comparative PFS of available treatments for R/R CLL. Indirect treatment comparisons suggest PFS on zanubrutinib may be superior to other BTKis and immunochemotherapies in R/R CLL patients.[Table: see text]
Characteristics of patients with hematologic malignancies without seroconversion post-COVID19 third vaccine dosing (3V): Real-world data from large midwestern healthcare system.
Authors: Sigrun Hallmeyer, Michael A. Thompson, Veronica Fitzpatrick, Yunqi Liao, Michael P. Mullane, Stephen Charles Medlin, Katherine Cleland, Tulio Rodriguez, Robert Citronberg, James L. Weese
Journal: Journal of Clinical Oncology (2022)

e19513 Background: Patients (Pts) with hematologic malignancies (HM) are at greater risk of severe morbidity and mortality caused by COVID19 and show a lower response to the two-dose COVID19 mRNA vaccine series. The primary vaccine series now includes a third dose of the COVID19 vaccine (3V) for immunocompromised Pts. The objective of this study was to explore the characteristics of HM patients who had no change in SARS-CoV-2 spike protein titer levels post 3V (-/-) to gain a better understanding of the drivers of serostatus. Methods: This retrospective cohort study analyzed Pt data on SARS-CoV-2 spike IgG antibody titers pre- and post- 3V across the healthcare system. This study included 268 fully vaccinated HM Pts diagnosed with HM between October 31, 2019 and January 31, 2022 and had a negative serostatus prior to 3V. Post 3V titers were obtained 21 days after 3V. Demographics, association between characteristics and seroconversion status, and odds ratios were all assessed (table). Results: Pts with Non-Hodgkin lymphoma (NHL) had 6 times the odds of not seroconverting compared to multiple myeloma (MM) (CI 1.88 – 19.12, P = .0010). NHL also have about 14 times the odds of not seroconverting compared to Pts diagnosed with other HM conditions, which included: neoplasms of uncertain behavior and disorders of white blood cells (CI 1.72 – 112.44, P = .0021). 90% of seronegative Pts showed no spike IgG antibody reaction to 3V as indicated by pre- and post- 3V index values. Demographics, previous COVID19 infection, and vaccine type were not significantly associated with seroconversion. Conclusions: HM patients who are not seroconverting after 3V, suggest a prioritized population for continued increased behavioral precautions, additional vaccination efforts, including a fourth dose of an mRNA COVID19 vaccine, as well as passive immunity boosting through monoclonal and polyclonal antibodies.[Table: see text]
OTHR-22. Malignant mesothelioma (MM) as second cancer in childhood brain tumor survivors: the first child with neurofibromatosis type 2 and concurrent MM
Authors: Marco Crocco, Antonio Verrico, Patrizia De Marco, Marzia Ognibene, Valeria Capra, Ferruccio Romano, Cristina Moreiro, Elisa Bennicelli, Nunzio Salfi, Salvina Barra, Francesca Rizzo, Andrea Rossi, Claudia Milanaccio, Maria Luisa Garrè, Gianluca Piccolo
Journal: Neuro-Oncology (2022)

Abstract We report two cases of malignant mesothelioma (MM) in childhood brain tumor survivors. A 40-year-old man, who was treated at the age of ten with chemotherapy and craniospinal radiotherapy (up to 54.5 Gy) for a pineal secreting non-germinomatous germ cell tumor, had persistent fever, fatigue, and weight loss. A total body CT scan revealed several pulmonary and abdominal wall nodularities. The histological examination on a biopsy diagnosed a biphasic MM. The karyotype and array-CGH of peripheral blood were normal; a FISH of tumor cells showed a breakage of locus EWSR1 (22q12.2). In this case, environmental exposure was identified (asbestos in public water tanks). His MM followed an aggressive course and resulted in death after three months. A twelve-year-old boy affected by severe neurofibromatosis type 2 (NF2) already treated with several neurosurgical exeresis and chemotherapy lines (hydroxycarbamide, bevacizumab, sirolimus), developed multiple abdominal lesions, associated with pleural effusion and weight loss. The CT scan showed the thickening of the left pleura and multiple peritoneal nodules. The cytological examination on thoracentesis diagnosed an epithelioid MM. The karyotype on paracentesis-obtained cells revealed monosomy of chromosomes 14 and 22, loss of Y, and trisomy of 6, 10, 11, 16, and 20. NGS is currently ongoing to exclude germline or somatic second hits. Importantly, no exposure to asbestos was found. Less than 2% of MMs occur below 45 years of age; it is a rare secondary tumor in cancer survivors and environmental or genetic contributing causes are often detectable on a careful investigation. Variants in NF2 are considered to be the second most common after those in BAP1. To our knowledge, this is the first child with NF2 and concurrent MM reported to date. Compared to the expected prognosis, his MM has followed a mild course, and one year after diagnosis he is still alive.
Management of infliximab-refractory immune checkpoint inhibitor gastrointestinal toxicity: A multicenter case series.
Authors: Catriona Harvey, Kazi Jannatun Nahar, Serigne N. Lo, Tasnia Ahmed, Sheima Farag, Nadia Yousaf, Kate Young, Liselotte Tas, Aafke Meerveld-Eggink, Christian U. Blank, Austin Thomas, Jennifer Leigh McQuade, Bastian Schilling, Douglas Buckner Johnson, Roberto Martin Huertas, Ana Maria Arance, Joanna Lee, Lisa Zimmer, Georgina V. Long, Alexander M. Menzies
Journal: Journal of Clinical Oncology (2022)

2665 Background: Immune checkpoint inhibitor (ICI) GI tox (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab (IFx); however not all pts respond and best management of IFx-Refractory ICI GI toxicity (IRIGItox) is not clear. Methods: We conducted an international multi-centre retrospective case series. IRIGItox was defined as failure of symptom resolution ≤ Gr 1 (CTCAE v5.0) following ≥ 2 IFx doses or failure of symptom resolution ≤ Gr 2 after 1 dose. Data were extracted regarding demographics, steroid use, response and survival. Tox was graded at symptom onset and time of IFx failure. Efficacy of IFx refractory therapy was assessed by symptom resolution, time to resolution and steroid wean. Results: 78 pts were identified; med age 60 yrs (95% CI 56-65), 56% male. 70 (90%) had melanoma, 55 (71%) had advanced-stage, 60 (77%) received anti-CTLA-4 (with anti-PD1 50, single agent 10). Most had colitis (N=75, 96%) and ≥ Gr 3 tox (N=74, 95%) at symptom onset. Pre-IFx investigation varied: imaging 37%; faecal calprotectin 29%; endoscopy 59%. All pts received Med time to steroid initiation was 3 days (95% CI 2-4). 46 (59%) had primary steroid refractory disease,. Med time from symptom onset to IFx was 18 days (95% CI 12-23), a med 2 (range 1-6) doses of IFx were given, 69 (88%) pts received &gt; 1 IFx dose. Across 78 pts, 105 post IFx treatments were given: calcineurin inhibitors (ciclosporin, tacrolimus, 32); antimetabolites (mycophenolate, azathioprine, 26); non-TNF-α MABs (vedolizumab, ustekinumab, 20); non-targeted anti-inflammatory (mesalazine, 16); non-pharmacological (colectomy 5, faecal transplant 1, photophoresis 1). 4 pts did not receive therapy for IRIGItox. Of these, 2 died of melanoma prior to resolution of tox; 1 had resolution after 4 doses IFx, 1 had recurrent melanoma and flare of tox on PD1 re-challenge. IRIGItox outcomes by post IFx treatment are shown in Table. Conclusions: This retrospective case series confirms heterogeneous management of IRIGItox. Non-pharmacological interventions and calcineurin inhibitors appear most likely to result in tox resolution. Calcineurin inhibitors have the shortest time to resolution in responders. Further details on post-IFx management and oncological outcomes will be examined. [Table: see text]
Immunotherapy with nivolumab after progression on lenvatinib in advanced hepatocellular carcinoma: A real-world Indian experience.
Authors: Amit Rauthan, Poonam Patil, Nitin Yashas Murthy, S.P. Somashekhar, Shabber Zaveri, Rajashri Aswath, Prathyush V, Chinnu Jomi
Journal: Journal of Clinical Oncology (2022)

e16117 Background: Firstline treatment of advanced hepatocellular carcinoma (HCC) till recently has been sorafenib or lenvatinib. Lenvatinib, due to its better tolerability and efficacy (in PFS) over sorafenib, is our preferred first line treatment. Nivolumab, with an objective response rate (ORR) of 14.3% and median duration of response of 16.6 months, was approved by FDA on the basis of the CheckMate-040 trial in patients who progressed or were intolerant to sorafenib. There is very limited data of immunotherapy on progression with lenvatinib. Methods: This is a single center, retrospective analysis of patients with advanced HCC who progressed on first line lenvatinib and received treatment with nivolumab. The endpoints were objective response rate (ORR), progression free survival (PFS), overall survival (OS) and toxicity. Results: 15 patients who progressed on lenvatinib, received nivolumab at 3 mg/kg, 2 weekly as second line therapy between July 2019 to July 2021. There were 2 females and 13 males. Median age was 66 years (37-77 years). All patients were BCLC stage C. AFP was elevated in 11 patients. Child Pugh score was A in 10 patients, and B in 5 patients. 7 patients had background of hepatitis B and 1 had hepatitis C. The number of cycles of nivolumab ranged from 2 to 13 cycles. 3 patients (20%) had partial response, 2 had stable disease and 10 (66.6%) had progressive disease by recist criteria. The ORR was 20% and median PFS was 3 months. Median OS was 8 months. The common side effects were hypothyroidism in 7 (46.6%), fatigue in 4 (26.6%) and skin rashes in 3 (20%) patients. Conclusions: Immunotherapy with nivolumab showed limited efficacy in our patients of HCC who have progressed on lenvatinib. There were few patients who showed durable response, but there are no biomarkers to choose these patients. The immune related side effects were manageable. With the first line approval of combination therapy with atezolizumab and bevacizumab, single agent second line immunotherapy with its limited efficacy, may have a reduced role in HCC management.
Impact of diagnostic and end-of-induction Curie scores in tandem autologous hematopoietic cell transplant for patients with high-risk neuroblastoma: A report from the Children’s Oncology Group.
Authors: Keri A. Streby, Marguerite T. Parisi, Barry L. Shulkin, Brian LaBarre, Rochelle Bagatell, Lisa Diller, Stephan A. Grupp, Katherine K. Matthay, Stephan D. Voss, Alice L. Yu, Wendy B. London, Julie R. Park, Gregory A. Yanik, Arlene Naranjo
Journal: Journal of Clinical Oncology (2022)

10027 Background: Diagnostic mIBG (meta-iodobenzylguanidine) scans are an integral component of response assessment in children with high-risk neuroblastoma. The role of end of induction (EOI) Curie Scores (CS) has been previously described in patients undergoing a single autologous hematopoietic cell transplant (AHCT) as consolidation therapy. We now examine the prognostic significance of CS in patients randomized to tandem or single AHCT on the Children’s Oncology Group (COG) trial ANBL0532. Methods: A retrospective analysis of mIBG scans obtained from patients enrolled in COG ANBL0532 (n = 652) was performed. Evaluable patients (n = 179) had mIBG-avid, International Neuroblastoma Staging System (INSS) stage 4 disease, did not progress during induction therapy, consented to consolidation randomization, and received either a single (n = 99) or tandem AHCT (n = 80). In addition, evaluable patients had paired mIBG scans at time of initial diagnosis and EOI. Optimal CS cut points maximized the outcome difference (≤ vs &gt; CS cut-off) according to the Youden index. Log-rank tests compared EFS subgroups, with p &lt; 0.05 considered statistically significant. 3-year EFS is presented ± standard error. EFS was estimated for relative reductions in CS of 50% and 75% from diagnosis to EOI. Results: For recipients of tandem AHCT, the optimal cut point at diagnosis was CS = 12, with superior EFS from study enrollment for patients with CS&lt;12 (74.2±7.9%; n = 31) vs CS &gt; 12 (59.2±7.1%; n = 49) (p = 0.002). At EOI, the optimal cut point was CS = 0, with superior EFS from EOI for patients with CS = 0 (72.9±6.4%; n = 48) vs CS &gt; 0 (46.5±9.1%; n = 32) (p = 0.002). The cut point at diagnosis for recipients of single AHCT was CS = 21 (p = 0.04), while the EOI CS had an optimal cut point of 2, but without a significant difference in EFS (p = 0.29). Absolute CS at diagnosis and at EOI had a greater impact on outcome than the relative reduction in CS between diagnosis and EOI, for both single and tandem AHCT. Conclusions: In the setting of tandem transplantation for children with high-risk neuroblastoma, Curie scores at diagnosis and end-induction may identify a more favorable patient group. Patients treated with tandem AHCT who exhibited a CS&lt;12 at diagnosis or CS = 0 at EOI had superior EFS compared to those with CS above these cut points. Similar to prior reports, a CS&lt;2 was the optimal cut point for single transplant recipients. Clinical trial information: NCT00567567.
Evaluation of homologous recombination deficiency biomarkers in patients with ovarian cancer treated with PARP inhibitors.
Authors: Leticia Campoverde, Laercio Lopes Da Silva, Hyan Silveira, Wilson Coelho Nogueira, Lida A. Mina, Gilberto Lopes, Felipe Batalini
Journal: Journal of Clinical Oncology (2022)

e17615 Background: Germline BRCA1/2 mutations are associated with response to Poly(ADP-ribose) polymerase inhibitors (PARPi). In addition to BRCA1/2 mutations, there are other Homologous Recombinations Deficiency (HRD) biomarker candidates already available in clinical practice including genome-wide loss-of-heterozygosity (gLOH) and myChoice score. Inconsistencies in biomarkers used in clinical trials with PARPi are a challenge to clinical interpretation. This study aims to compare clinically available HRD biomarkers in terms of benefits from PARPi. Methods: We performed database search for phase II or III randomized clinical trials comparing PARPi versus chemotherapy, and meta-analysis using generic inverse variance and a random-effects model. Patients were classified into three categories according to their HRD status: 1) BRCAmut (patients with BRCA1/2 mutation of germline or somatic origin), 2) non-BRCA HRD (patients BRCA wild-type (wt) with a different HRD biomarker - gLOH or myChoice); and 3) homologous recombination proficiency (HRP) (BRCAwt and without HRD biomarkers). From those that were BRCAwt, we compared myChoice+ with gLOH-high. Results: Eight studies (n = 4372 patients) with PARPi as first-line and recurrence settings were included. BRCAmut had PFS HR 0.29 (95%CI, 0.24-0.35), BRCAwt &amp; HRD 0.43 (95%CI, 0.34-0.53) and HRP 0.74 (95%CI, 0.62-0.89). In a secondary analysis by HRD stratification method, patients with BRCAwt &amp; myChoice &gt; = 42 had PFS HR 0.43 (95%CI, 0.34-0.56), similar to patients with BRCAwt &amp; gLOH-high with PFS HR 0.42 (95%CI, 0.28-0.62). Conclusions: Patients with BRCA mutations benefited the most from PARPi. From patients with BRCA1/2 wild-type, a similar benefit was found in patients with gLOH-high and those myChoice+, which was superior to HRP patients. The clinical development of further HRD biomarkers (i.e. Sig3, HRDetect) may help identify more patients who benefit from PARPi.
Genome-wide Enrichment of <i>TERT</i> Rare Variants in Idiopathic Pulmonary Fibrosis Patients of Latino Ancestry
Authors: David Zhang, Qi Li, Gundula Povysil, Chad A. Newton, Toby M. Maher, Philip L. Molyneaux, Imre Noth, Fernando J. Martinez, Ganesh Raghu, Jamie L. Todd, Scott M. Palmer, Adam Platt, Slavé Petrovski, David B. Goldstein, Christine Kim Garcia
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease characterized by progressive fibrosis and irreversible decline in lung function.Genome-wide rare variant studies have either included only patients of European ancestry (1, 2) or have been disproportionally enriched with patients of European ancestry so that rare variant genetics of patients of non-European ancestry with IPF have been understudied.In this report, we evaluate the enrichment of rare genetic variants in patients of non-European ancestry with IPF. PatientsThis study was approved by the Institutional Review Board at Columbia University, and written consent was obtained from all participants.Detailed information regarding patient and control cohorts, including enrollment and sequencing sites, was previously published (3).Briefly, all case subjects carried a diagnosis of IPF or familial pulmonary fibrosis.The full cohort included multiethnic, unrelated cases (n = 2,966) and control subjects (n = 29,817) (3). Methods
Pilot study of a text messaging-integrated and Chatbot-interfaced self-management program for symptom control in GI cancer patients undergoing chemotherapy.
Authors: Kuang-Yi Wen, Sameh Gomaa, Max Schnoll, Tingting Zhan, Babar Bashir, James Posey
Journal: Journal of Clinical Oncology (2022)

e24117 Background: Chemotherapy treatments are increasingly provided in the outpatient setting. Patients are expected to monitor and manage a range of diverse and complicated side-effects without readily accessible clinical support. The overall goal of this study is to address the gap in continuity of care during outpatient chemotherapy through the integration of an innovative text messaging system with a Chatbot interface in the real-time monitoring and proactive management of side-effects among gastrointestinal (GI) cancer patients undergoing IV chemotherapy. Methods: Real-time chemotherapy-associated side effects monitoring supportive system (RT-CAMSS) was iteratively developed with patient-centered inputs and evidence-based and theory-guided information to address chemotherapy knowledge, self-care symptom management skills, emotional support, doctor-patient communication, and nutritional and physical activity suggestions. We conducted a single-arm 2-month pilot study, in which GI patients undergoing chemotherapy received two intervention text messages per week and a weekly CTCAE-based symptom assessment delivered through Chatbot interface with tailored feedback. Baseline and post-intervention patient-reported outcome follow-up surveys were collected. Results: 45 eligible patients were approached and 34 consented and enrolled (76% consenting rate). The mean age was 61 (±12). 56% were females and 61.8% were non-Hispanic White. The most frequent cancer type was pancreatic cancer (53%), followed by colon cancer (35%). 27 participants completed the post-intervention follow up (79% retention rate)..Functional wellbeing subscale of the FACT instrument showed significant improvement from baseline to 2 month ( p &lt; 0.05). 27 participants responded to the weekly Chatbot-interfaced symptom assessment at least once (79% feasibility rate). The most frequent reported symptom collected from Chatbot assessment was constipation (50%), followed by weight loss (35%) and fatigue (32%). Post-intervention open-ended satisfaction survey found that participants perceived the intervention easy to use with helpful information. Conclusions: Communication via mobile technologies is highly scalable for improving health services. The study provides preliminary evidence of engagement, acceptability and benefits of RT-CAMSS, which should be evaluated in a controlled clinical trial.
Isolation and culture of circulating pancreatic cancer tumor cells using a microfilter.
Authors: Atsuko Furukawa, Osamu Shimomura, Kazuhisa Araki, Tomoko Mori, Tatsuya Oda, Satoshi Matsusaka
Journal: Journal of Clinical Oncology (2022)

e16230 Background: The presence and number of circulating tumor cells (CTCs) are reportedly associated with prognosis but the rarity of CTCs in peripheral circulation limits the ability of conventional technologies to provide fully accurate analyses. The purpose of this study was thus to establish a novel approach to capture and culture the CTCs using a microfilter device. Methods: This was a prospective study in preoperative patients with pancreatic cancer at the University of Tsukuba Hospital after approved by the Institutional Review Board. Five ml of whole blood was collected from each patient into an EDTA-treated collection tube before pumping through an 8μm pore microfilter. Cells isolated on the filter were stained with PE-conjugated anti-EpCAM, FITC-conjugated anti-CD45 and Hoechst 33342. The filter was then transferred to a 35mm dish and cultured with 20%FBS-IMDM-F12 medium containing 2%Matrigel- EGF-FGF-B27 for 4-6 weeks. Cells were visualized with an automatic fluorescence microscope. A CTC was defined as an intact round oval cell with a visible nucleus, positive staining for EpCAM and negative staining for CD45. Results: A total of 9 patients [male/female; 4/5, median age;71 (39-78), Stage 0/IA/IIA/IIB; 1/3/3/2, preoperative chemotherapy/chemoradiation; 1/2] were enrolled. CTCs were captured in 8 out of 9 cases and cultured CTCs were kept viable for 4-6 weeks in 6 out of 9 cases. CTCs formed colonies by 4-6 weeks of culture, colonies were expanding and blood cells disappeared. No cultured CTCs were observed in the two cases who received preoperative chemotherapy. Conclusions: We successfully developed a novel culture method of patient CTC using a microfilter device. Our system supports the possibility of accurate detection and proliferation of CTCs on microfilters. Cultured CTCs could be used for patient-specific drug susceptibility testing and mutational profiles for future cancer patients.